Optimal Cytoreductive Surgery Research Articles

Impact of ascites volume on clinical outcomes in ovarian cancer: A cohort study

ObjectivesTo investigate the impact of ascites volume on ovarian cancer outcomes. MethodsClinicopathologic features of a cohort of patients with ovarian cancer were obtained from a curated database at a single institution. Progression free survival (PFS) and overall survival (OS) were recorded. Ascites volume at primary surgery was dichotomized at 2000mL and comparisons for high and low volume ascites were made. Additionally, to elucidate interactions between ascites and ovarian tumor progression, we evaluated the effect of intraperitoneal administrations of murine cell-free ascites versus saline in a syngeneic mouse model of epithelial ovarian cancer. ResultsOut of 685 patients identified, 58% had ascites present at the time of initial surgery. Considering the volume of ascites continuously, each liter of ascites was associated with shorter PFS (HR=1.12, 95% CI: 1.07–1.17) and OS (HR=1.12, 95%CI: 1.07–1.17). Patients with ascites greater than the median of 2000mL had significantly shorter PFS (14.5months vs. 22.7months; p<0.001) and OS (27.7months vs. 42.9months; p<0.001). After adjusting for stage, presence of ascites was inversely associated with ability to achieve optimal cytoreductive surgery. Consistent with these correlative results in patients, intraperitoneal administrations of murine cell-free ascites accelerated ovarian cancer progression in mice. ConclusionsThe volume of ascites at initial diagnosis of ovarian cancer correlated with worse PFS and OS. The effect of large volume on prognosis is likely to be in part related to reduced likelihood for complete resection of tumor (R0). If these findings are confirmed in independent studies, consideration should be made to add the presence of large volume ascites at diagnosis to the staging criteria for ovarian cancer.

Intraperitoneal chemotherapy following neoadjuvant chemotherapy and optimal cytoreductive surgery

Intraperitoneal chemotherapy following neoadjuvant chemotherapy and optimal cytoreductive surgery

Randomized trial of hyperthermic intraperitoneal chemotherapy (HIPEC) in women with primary advanced peritoneal, ovarian, and tubal cancer.

5520 Background: Cytoreductive surgery followed by taxane and platinum-based chemotherapy is standard treatment for advanced ovarian cancer. We compared results of randomly allocated HIPEC in primary advanced epithelial ovarian cancer who have optimal cytoreductive surgery in this prospective randomized multicenter trial. The study endpoint is to evaluate progression free survival (PFS) and overall survival (OS). Methods: 184 patients staged III and IV were randomly allocated to trial arm (HIPEC, cisplatin 75 mg/m2, 90 min) or control arm (no HIPEC), intraoperatively based on residual tumor (size &lt;1cm) from July 2010 to January 2016. The groups were well balanced according to the age, body mass index, performance status, stage, histology, serum CA125 level, and use of neoadjuvant chemotherapy (NAC) at study entry. Results: 184 pts (HIPEC, 92; control, 92) were included in this preplanned analysis. No mortality after surgery ± HIPEC was identified in both groups. Postoperative outcomes including extent of surgery, estimated blood loss, residual tumor, and hospitalization day were not different between both group, except operation time (487 vs. 404 min, p&lt;0.001) due to HIPEC procedure. The most common adverse event was anemia: 67.4% in HIPEC and 50% in control group (p=0.025). The other toxicity common in HIPEC group is the elevation of creatinine (15.2% vs. 4.3%, p=0.026). There were no differences between both groups for transfusion (35.9 vs. 29.3, p=0.432), neutropenia (19.6 vs. 10.9%, p=0.151), and thrombocytopenia (9.8 vs. 3.3%, p=0.136). Two-year PFS was 43.2% and 43.5% and 5-year PFS was 20.9% and 16.0% in HIPEC and control group, respectively (p=0.569). Five-year OS was 51.0% and 49.4% in HIPEC and control group, respectively (p=0.574). In women who received NAC, the median PFS for HIPEC and control group were 20 and 19 months, respectively (log-rank test, p = 0.137) and the median OS for HIPEC and control group were 54 and 51 months, respectively (log-rank test, p = 0.407). In the subgroup with NAC, 2-year PFS was 37.2% in HIPEC group and 29.5% in control group and 5-year OS was 47.9% in HIPEC group and 27.7% in control group. After 20 months in PFS and 30 months in OS, two survival curves in women who received NAC showed the trend of gradual distinction, favoring HIPEC group. Conclusions: No mortality was identified and postoperative morbidities were not statistically different between two groups except anemia and creatinine elevation in HIPEC group. The survival analysis did not show the statistical superiority of the HIPEC arm. More follow-up is required to confirm the impact of HIPEC on long-term survival outcome in ovarian cancer, especially in NAC group. Clinical trial information: NCT01091636.

The Effect of Para Aortic Lymph Node Dissection in Staging and Complete Cytoreductive Surgery of Ovarian Cancer

Objective: Lymphatic spread is a common feature of ovarian cancer both in early and advanced stages of the disease. There is also a controversial problem of the impact of para-aortic lymph node dissection between gynecologist oncologist experts. The aim of this study is evaluating the effect of Para aortic Lymph node dissection in ovarian cancer patients. Methods: This descriptive cross-sectional study was performed on 100 ovarian cancer patients admitted in department of gynecology oncology of Ghaem hospital, Mashhad University of Medical Sciences, Iran, from November 2013 - 2014. All patients underwent surgical staging surgery and optimal debulking surgery as possible. In addition, concurrent systematic pelvic and para-aortic lymphadenectomy up to the level of inferior mesenteric artery was performed. Results: A total of 100 patients were studied. The mean age was 47 years (SD = 13). In 73 patients optimal cytoreductive surgery was done with para aortic lymphadenectomy. 53 cases (72.6%) were in primary cytoreductive surgery and 20 cases (27.3%) in interval debulking surgery groups. Positive paraaortic lymph node in the first group was 6 cases (11.3) and in the second group was 2 cases (10%). 27 patients were in apparent stage I and 46 patients were in stage II-III-IV of disease. We found positive paraaortic lymph node in 11% of total patients. We found positive paraaortic lymph node without positive pelvic lymph node in two patients. Conclusions: Lymph node dissection will produce a significant benefit in accurate and complete surgical staging; it will reduce residual disease and then progression-free survival.

Difficulty in diagnosis and different prognoses between colorectal cancer with ovarian metastasis and advanced ovarian cancer: An empirical study of different surgical adoptions

ObjectiveTo determine the clinical manifestations and optimal management of female patients with advanced colorectal cancer (CRC) metastasis in ovaries mimicking advanced ovarian malignancy. Materials and MethodsA retrospective medical records review of female patients with primary CRC metastasis to ovaries, which were initially diagnosed as ovarian malignancy, and treated between 2001 and 2013. Clinical presentations, pathologic findings, and treatment outcomes were analyzed. ResultsIn total, 19 cases were collected in the study through a hospital tumor registry. The mean age of the patients at the time of diagnosis was 45 years (range, 28–63 years). The most common symptoms were abdominal pain or increased abdominal girth (63%). None of them had rectal bleeding. The ratio of cancer antigen-125 to carcinoembryonic antigen was available in 13 out 19 patients (less than 25 in 76.9%). Barium enema or colonoscopic exam was only performed in 10 outpatients. None of them had a positive finding. All 19 patients went for surgery, all of them had ovarian metastasis but only eight of them had bilateral involvement, and 14 of them had carcinomatosis. All patients went for either optimal cytoreduction surgery or suboptimal cytoreduction surgery. The patients who received optimal cytoreduction surgery had a significant better progression-free and overall survival than those who did not. ConclusionClinical manifestations of primary CRC with ovarian metastasis may be confused with advanced ovarian cancer. Negative barium enema or colonoscopic exam cannot rule out the possibility of CRC. For patients with a cancer antigen-125 to carcinoembryonic antigen ratio less than 25, 76% are good reference of CRC metastasis to ovaries. Optimal cytoreduction surgery like that used for treating advanced ovarian cancer had a better prognosis than suboptimal cytoreduction colorectal cancer treatment.

The role of splenectomy and distal pancreatectomy as cytoreductive procedures in ovarian cancer patients with upper abdominal involvement

Ovarian cancer has the highest mortality rate of all gynecologic cancers as 62% of cases are diagnosed at an advanced stage. The main concern in the surgical management of ovarian cancer is to achieve optimal cytoreductive surgery. Effective cytoreductive surgery at the time of initial therapy has been identified as the most important prognostic factor in the management of advanced ovarian cancer. This aggressive approach can cause unusual surgical management modalities including diaphragm stripping/resection, bowel resection, hepatic resection and splenectomy. Thus, splenectomy occasionally happens to be part of the ovarian cancer surgery. The indications and technique of splenectomy and distal pancreatectomy as cytoreductive procedures in ovarian cancer patients were described. The authors have presented the indications and techniques of splenectomy and distal pancreatectomy as cytoreductive procedures in ovarian cancer patients. Intraoperative and postoperative complications were reported in this study.

Beyond the Beyond: First Case of 9 Cytoreductive Surgeries in a Long-Surviving Ovarian Cancer Patient: Case Report

The role of surgery in recurrent ovarian cancer (ROC) is debated. Multiple prospective and retrospective series reported improved survival with optimal secondary surgical cytoreduction, but definitive results from randomized trials are needed. Up to the fourth cytoreductive surgery for recurrent disease in an attempt to improve patients' prognosis has been reported. We report the first case of multiple ROC in an Italian woman, 50 years old at diagnosis, who underwent 9 cytoreductive surgeries during her 17 years of disease with no serious postoperative complications. Multiple surgeries should not be considered as the standard treatment for ROC. In carefully selected patients, optimal cytoreductive surgery performed by highly specialized gynecologic oncologists might represent a useful tool in adjunction to chemotherapy for the management of ROC.

What Characterizes Long-term Survivors of Recurrent Ovarian Cancer? Case Report and Review of the Literature.

Women with recurrent ovarian cancer have a poor prognosis and short survival. However, some women are long-term survivors and it is unclear whether they share specific common characteristics. We present the case of a 63-year-old woman with histologically-proven recurrent ovarian cancer and a survival time of 16 years after the diagnosis of recurrence. She underwent initial debulking surgery in 1994, followed by 6 cycles of adjuvant chemotherapy with cisplatin and paclitaxel. After recurrent disease was diagnosed by re-laparotomy in 2000, she underwent four lines of systemic chemotherapy from 2000 to 2009 (carboplatin/paclitaxel, topotecan, etoposide/treosulfan and liposomal doxorubicin) and four lines of endocrine therapy between 2002 and 2014 (tamoxifen, goserelin, tamoxifen and exemestane). In 2014, she underwent secondary debulking surgery and was tumor-free until 2015. Upon progression, she was then started on the fifth-line of endocrine therapy, fulvestrant, which was changed to the mTOR inhibitor everolimus in June 2016. In a PUBMED literature search, 360 cases of long-term survivors of recurrent ovarian cancer (LTSROC), defined as women with survival >5 years after the diagnosis of recurrence, were identified with a mean post-recurrence survival time of 7.5 years. Comparing the patient and therapy details of these women, we identified common characteristics of LTSROC, i.e. young age and optimal debulking at initial surgery, a long time span between first-line therapy and first recurrence and the combined use of optimal cytoreductive surgery and systemic chemotherapy. LTSROC are rare, with 360 cases described in the literature. LTSROC are characterized by young age, low tumor stage, long recurrence-free interval and combined modality treatment with optimal cytoreductive surgery and systemic chemotherapy.

CT in ovarian cancer staging: how to review and report with emphasis on abdominal and pelvic disease for surgical planning.

CT of the abdomen and pelvis is the first line imaging modality for staging, selecting treatment options and assessing disease response in ovarian cancer. The staging CT provides disease distribution, disease burden and is the imaging surrogate for surgico-pathological FIGO staging. Optimal cyto-reductive surgery offers patients’ the best chance for disease control or cure, but sub-optimal resection confers no advantage over chemotherapy and adversely increases the risk of post surgical complications. Although there is extensive literature comparing performance of CT against laparoscopy and surgery, for the staging abdominal and pelvic CT, there are currently no accepted guidelines for interpretation or routinely used minimum data set templates for reporting these complex CT scans often with extensive radiological findings. This review provides a systematic approach for identifying the important radiological findings and highlighting important sites of disease within the abdomen and pelvis, which may alter or preclude surgery at presentation or after adjuvant chemotherapy. The distribution of sites and volume of disease can be used to categorize patients as suitable, probably suitable or not suitable for optimal cyto-reductive surgery. This categorization can potentially assist oncological surgeons and oncologists as a semi objective assessment tool useful for selecting patient treatment, streamlining multi disciplinary discussion and improving the reproducibility and correlation of CT with surgical findings. The review also highlights sites of disease and complications of ovarian cancer which should be included as part of the radiological report as these may require additional surgical input from non gynaecological surgeons or influence treatment selection.

Primary cytoreductive surgery and adjuvant hormone therapy in women with advanced low-grade serous carcinoma: Reducing overtreatment without compromising survival?

Objectives: Women with low-grade serous carcinoma (LGSC) of the ovary or peritoneum have low chemotherapy response rates and poor overall survival (OS) with advanced-stage disease. Most LGSC tumors overexpress hormone receptors, which represent a potential treatment target. Our study objective was to determine the safety and survival outcomes of patients with advanced-stage LGSC treated with cytoreductive surgery (CRS) and hormone therapy (HT) in the primary setting. Methods: A retrospective study at two academic cancer centers was performed. Patients with stage II–IV LGSC underwent either primary or interval CRS, followed by adjuvant HT, between 2004 and 2014. Expert gynecologic pathologists reviewed all cases. Data on patient, surgical, and treatment variables were collected. Median progression-free survival (PFS) and OS were calculated. Outcomes were compared with those of an age- and stage-matched LGSC control group treated with CRS and chemotherapy. Results: Twenty-six patients with LGSC were treated with CRS + HT. Primary CRS + HT was administered in 25 patients, and neoadjuvant chemotherapy followed by CRS + HT was administered in 1 patient. The median patient age was 46.5 years, and patients had stage II (n = 4), stage IIIA (n = 6), stage IIIC (n = 15), and stage IV (n = 1) disease. Optimal CRS to no apparent gross residual disease was achieved in 81.5%, optimal CRS less than 1 cm in 14.8%, and suboptimal CRS in 3.7%. The patient treated with neoadjuvant chemotherapy had extensive carcinomatosis and liver metastases (stage IV) that progressed with chemotherapy; after CRS, she has been progression-free for 15 months with shrinking liver implants on HT. Anastrozole was administered postoperatively in 55.6%, letrozole in 37.0%, and tamoxifen in 7.4%. The median time for HT was 18 months. After a median follow-up of 28 months (range, 10–126 months), 4 patients (14.8%) developed a recurrence. All initial abdominopelvic recurrences were salvaged with CRS with or without chemotherapy or HT. Three patients (11.5%) are alive with disease, and 23 (88.5%) have no evidence of disease. The median PFS was 22 months and median OS was not yet reached. Compared with a control group of 44 patients with LGSC treated with CRS + chemotherapy (median PFS: 21 months, median OS: 70 months), the survival of the HT-treated cohort was not significantly different. Conclusions: Our series describes the initial experience with CRS and HT for primary advanced-stage LGSC. Although surgery remains the mainstay of therapy, cytotoxic chemotherapy may not be necessary in the primary setting. These results merit further investigation in a prospective trial.

Cited rationale for variance in the use of primary intraperitoneal chemotherapy following optimal cytoreduction for stage III ovarian carcinoma at a high intraperitoneal chemotherapy utilization center

ObjectiveStudies have demonstrated improved ovarian cancer survival with the administration of a combination of intravenous (IV) and intraperitoneal (IP) chemotherapy following optimal cytoreduction. Despite this, IV/IP chemotherapy is not uniformly used. In this retrospective cohort study, we assessed the documented reasons for giving IV-only chemotherapy. MethodsAll patients who had optimal primary cytoreductive surgery for stage III ovarian, fallopian tube, or primary peritoneal carcinoma, met eligibility criteria for GOG-172, and received primary chemotherapy at our institution between 2006 and 2013 were identified. Patients who received at least one cycle of adjuvant IV/IP therapy were included in the IP group. Patient characteristics, treatment information, and reason cited for not administering IP therapy were collected. ResultsOf the patients evaluated, 330 met inclusion criteria. The majority (n=261, 79%) received at least one IV/IP cycle (median, 6; range, 1–6), and 62% completed 6cycles. The most common reason for giving IV-only therapy was postoperative status (i.e., delayed wound healing, performance status), accounting for 18 (26%) of the 69 IV-only patients (5% of the entire cohort). Other cited reasons were baseline comorbidities (15%) and IP port complications (12%). Receipt of ≥1cycle of IP chemotherapy (HR 0.51; 95% CI, 0.32–0.80) and no gross residual disease (HR 0.47; 95% CI, 0.31–0.71) were associated with improved overall survival. ConclusionPotentially modifiable factors identified as leading to the use of IV-only chemotherapy were postoperative status and IP port complications, which if altered, could potentially lead to increased IP chemotherapy use.

Long-term Benefit of Tumor Volume-Directed Involved Field Radiation Therapy in the Management of Recurrent Ovarian Cancer.

This study aimed to report on long-term effectiveness of involved field radiation therapy (IFRT) in the salvage of localized recurrent ovarian cancer (ROC). A retrospective analysis of 27 patients with a diagnosis of epithelial ovarian cancer who received tumor volume-directed IFRT for localized extraperitoneal recurrences (either as consolidation after cytoreductive surgery (CRS) or as attempted salvage if unresectable) forms the basis of this report. All patients were heavily pretreated with multiple chemotherapy regimens. Involved field radiation therapy was primarily with external beam (median dose, 50.4 Gy). Local recurrence-free survival (LRFS) was defined as freedom from in-field recurrences and was considered as a measure of effectiveness of radiotherapy. Statistical analyses evaluated association between disease-free survival, overall survival, LRFS, and various prognostic factors. Comparison was also made with a similar but unmatched cohort with localized recurrences salvaged by additional chemotherapy instead of local therapies (NIFRT group). Of 27 patients, 17 had optimal CRS before RT. The actuarial survival at 5 and 10 years (in parenthesis) from date of radiation were LRFS (70% and 60%), overall survival (30% and 19%), and disease-free survival (33% and 20%). None of the NIFRT patients survived beyond 5 years from initiation of salvage chemotherapy. Long-term follow-up in this selected series confirmed the benefit of IFRT (±CRS) in localized ROC. Chemotherapy salvage in a similar NIFRT group was not equivalent, suggesting a role for locoregional therapies in selected patients with ROC.

Optimal cytoreductive surgery in patients with advanced uterine carcinosarcoma: A multi-institutional retrospective study from the Japanese gynecologic oncology group

BackgroundThe benefits of cytoreductive surgery for uterine carcinosarcoma (UCS) are unknown. The objective of this study was to determine the impact of optimal surgery on advanced UCS patient survival. MethodsWe performed a multi-institutional, retrospective study of women diagnosed with stage IIIIV UCS between 2007 and 2012. Data were obtained retrospectively from medical records, including demographic, clinicopathologic, treatment, and outcome information. Optimal cytoreductive surgery was defined as surgery resulting in a maximum residual tumor of ≤1cm. The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS), and the Cox regression model was used to examine the impact of selected factors on survival. ResultsA total of 225 UCS patients (median age, 63years) were identified, including 136 (60%) with stage III and 89 (40%) with stage IV disease. Among these patients, 170 (76%) received optimal cytoreductive surgery. The median follow-up time was 19months. The median PFS was 11.5months (95% confidence interval [CI], 10.6–13.4) and 8.1months (95% CI, 5.1–9.5) for patients who received optimal and suboptimal cytoreductive surgery, respectively (P<0.0001). The median OS was 37.9months (95% CI, 28.3–not reached) and 18months (95% CI, 9.6–21) for patients who received optimal and suboptimal cytoreductive surgery, respectively (P<0.0001). Residual tumor >1cm was associated with worse OS while pelvic lymph node dissection was associated with improved OS. ConclusionOptimal cytoreductive surgery and pelvic lymph node dissection are associated with improved OS in advanced UCS patients.

Outcomes of advanced epithelial ovarian cancer with integration of metronomic chemotherapy: An Indian rural cancer centre experience.

Background:Paclitaxel-platinum and optimal cytoreductive surgery are the standard of care for ovarian carcinoma. Poor socioeconomic profile and therapeutic constraints in rural India poses a therapeutic challenge.Aim:To evaluate outcomes of epithelial ovarian carcinoma.Objectives:To calculate disease-free survival (DFS), overall survival (OS), and factors affecting outcomes.Materials and Methods:Data of patients diagnosed as ovarian carcinoma registered between March 2009 and March 2014 were retrieved. Demographic profile, chemotherapy and response, surgery, and disease progression were collected. Patients who underwent surgery or completed three cycles of chemotherapy were selected. Kaplan–Meir survival was used to determine disease-free and OS. Log-rank test used to evaluate factors affecting outcome.Results:Median follow-up is 26 months. 93/102 patients (91%) underwent cytoreductive surgery, of which 37 had primary cytoreduction (40%) while 56 had interval cytoreduction. 21/93 (23%), 57/93 (61%), and 15/93 (16%) patients were operated by local surgeons, surgeons of our hospital, and trained oncosurgeons, respectively. Induction paclitaxel-platinum was used in 35/63 (56%) patients while 28/63 patients (44%) received neoadjuvant metronomic chemotherapy. Median DFS and OS are 17 and 54 months respectively while 3 year OS of 66%. Median DFS of patients operated by oncosurgeons versus local surgeons were 22 months versus 15 months (P = 0.01), OS was 54 versus 26 months (P = 0.01).40/88 (45%) patients received maintenance metronomic therapy after adjuvant chemotherapy with median of 6 months (range 2–18 months). Patients receiving metronomic maintenance had better DFS, 18 months versus 15 months (P = 0.69).Conclusion:Induction therapy in ovarian carcinoma helps in selecting patients for cytoreductive surgery. Outcomes are better if operated by trained oncosurgeons. Maintenance metronomic has potential to delay disease progression.

Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy to Treat Advanced/Recurrent Epithelial Ovarian Cancer: Results from a Retrospective Study on Prospectively Established Database

BACKGROUND: Despite the best standard treatment, optimal cytoreductive surgery (CRS) and platinum/taxane-based chemotherapy, prognosis of advanced epithelial ovarian carcinoma (EOC) remains poor. Recently, CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC) has been developed to treat peritoneal carcinomatosis (PC). This study was to evaluate the efficacy and safety of CRS+HIPEC to treat PC from advanced/recurrent EOC. METHODS: Forty-six PC patients from advanced EOC (group A) or recurrent EOC (group B) were treated by 50 CRS+HIPEC procedures. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoints were safety profiles. RESULTS: The median OS was 74.0 months [95% confidence interval (CI) 8.5-139.5] for group A versus 57.5 months (95% CI 29.8-85.2) for group B (P = .68). The median PFS was not reached for group A versus 8.5 months (95% CI 0-17.5) for group B (P = .034). Better median OS correlated with peritoneal cancer index (PCI) < 20 (76.6 months for PCI ≤ 20 group vs 38.5 months for PCI > 20 group, P = .01), complete cyroreduction (residual disease ≤ 2.5 mm) [79.5 months for completeness of cytoreduction (CC) score 0-1 vs 24.3 months for CC 2-3, P = .00], and sensitivity to platinum (65.3 months for platinum-sensitive group vs 20.0 for platinum-resistant group, P = .05). Serious adverse events occurred in five patients (10.0%). Multivariate analysis identified CC score as the only independent factor for better survival. CONCLUSION: For advanced/recurrent EOC, CRS+HIPEC could improve OS with acceptable safety.

Carcinosarcoma of the ovary: a single institution experience and review of the literature.

To evaluate the management and outcome in patients with advanced stage primary carcinosarcoma (CS) of the ovary in a single institution. The authors performed a retrospective analysis of all patients treated for CS of the ovary between 1994 and 2011. The medical records, operative reports and pathology records were abstracted for baseline characteristics, surgical staging, degree of cytoreduction and chemotherapy regimens used. Standard statistical methods for analysis of the data were used. A total of 33 patients with ovarian CS were identified. Of these, 28 records were available for analysis. One patient was Stage I (3.5%), two were Stage II (11.1%), 20 were Stage III (71.4%), and five (17.9%) were Stage IV. The early stage (Stage I and II) patients were excluded from analysis. Of the 25 advanced stage (III and IV) patients, 21 (84.0%) were optimally cytoreduced to a residual disease of < one cm and four (16.0%) were suboptimally cytoreduced. The median progression free survival (PFS) and overall survival (OS) were ten and 21 months, respectively, for advanced stages. Twenty-one (75%) patients received adjuvant chemotherapy and 62% (13 of 21) of treated patients received paclitaxel/carboplatin (T/C) as first-line chemotherapy. The median PFS and OS were 15.6 and 31.7 months, respectively, for those treated with T/C. There was no.difference in PFS (p = 0.42) and OS (p = 0.91) between the patients who received T/C vs. other chemotherapy regimens as a first-line adjuvant chemotherapy. Patients with optimal cytoreduction had an improved PFS compared to those with suboptimal cytoreduction (ten vs. four monthsp = 0.015); however, there was no difference in OS (21 vs. 13 p = 0.117). The two-year OS was 48.0%. In the preset study, PFS was improved in patients who were optimally cytoreduced at the time of diagnosis. T/C is an active regimen in the treatment of ovarian CS and has the potential to be the backbone for addition of biologic targeted therapies in the future. For advanced ovarian CS the authors recommend optimal cytoreductive surgery followed by T/C chemotherapy.

Specific features of current intraperitoneal therapy in patients with ovarian cancer

Background. Today there are 3 trends in favor of intraperitoneal (IP) chemotherapy: maintenance of its potential 5- and 10-year survival benefit in patients with ovarian cancer (OC); advantages of the IP administration of drugs even after nonoptimal surgery; enhancement of the efficiency of chemotherapy irrespective of the number of IP treatment cycles. There is also an expanded list of possible IP medicines and incorporation of novel targeted drugs into treatment regimens. However, the long-expected data of the most recent randomized trial GOG 0252 have proven deplorable and led to the activation of discussions on the role of IP therapy. Objective: to generalize the experience of 4 oncology departments with IP therapy in patients with disseminated OC and to compare the findings with those obtained by the world’s leading medical centers. Materials and methods. The retrospective analysis included 76 patients with Stage IIIC OC who had received IP chemotherapy in accordance with 3 regimens. For standardization of IP treatment procedures, the investigators assessed the following indicators: age; tumor morphological type; surgical radicality; catheter model and port placement procedure; drug administration route; number of treatment cycles; efficiency of therapy from expert ultrasonographic findings and CA-124, HE4, CA-19.9 marker levels, time to disease progression. The analysis also involved adverse manifestations, methods of their correction and the reasons for early treatment discontinuation were separately reported. The obtained data were processed using standard statistical programs. Results . 55 of the 76 patients could complete more than 4 IP therapy cycles. Among them, only 4 patients were observed to have disease progression at follow-ups lasting over 24 months. Conclusion. Current IP therapy is a safe and convenient drug treatment in patients with OC after optimal cytoreductive surgery. The mastery and standardization of the procedures for surgery and placement of current IP Celsite® Peritoneal and Celsite® Drainaport devices make it possible to minimize adverse manifestations and to perform all planned therapy cycles in necessary mode, by giving 50 % of the optimally operated patients with OC (Stage IIIC) the chance to have a long-term progression-free survival that is over 2 years, as shown by our observations.

Frontline treatment of epithelial ovarian cancer.

This is a contemporaneous review of the frontline treatment of epithelial ovarian cancer (EOC), specifically on the importance of optimal surgical cytoreductive surgery, the pivotal role of platinum-based adjuvant chemotherapy (which encompasses intraperitoneal and dose-dense regimens) and the emergence of neo-adjuvant chemotherapy. Additionally, the benefit of concurrent and maintenance bevacizumab in the suboptimally debullked stage III and stage IV EOC setting is also reviewed. The article also discusses the increasing importance of prognostic and predictive molecular biomarkers in the future management of EOC.

Pathological Characterization of Ovarian Cancer Patients Who Underwent Debulking Surgery in Combination With Diaphragmatic Surgery: A Cross-Sectional Study.

Despite exhaustive efforts to detect early-stage ovarian cancers, greater than two-thirds of patients are diagnosed at an advanced stage. Although diaphragmatic metastasis is not rare in advanced ovarian cancer patients and often precludes optimal cytoreductive surgery, little is known about the mechanisms and predictive factors of metastasis to the diaphragm. Thus, as an initial step toward investigating such factors, the present study was conducted to characterize the pathological status of ovarian cancer patients who underwent debulking surgery in combination with diaphragmatic surgery.This is a retrospective and cross-sectional study of patients who underwent debulking surgery in combination with diaphragmatic surgery at our institution between January 2005 and July 2015. Clinicopathological data were reviewed by board-certified gynecologists, pathologists, and cytopathologists. The rates of various pathological findings were investigated and compared by Fisher exact test between 2 groups: 1 group that was pathologically positive for diaphragmatic metastasis (group A) and another group that was pathologically negative for diaphragmatic metastasis (group B).Forty-six patients were included: 41 patients pathologically positive and 5 pathologically negative for diaphragmatic metastasis. The rates of metastasis to the lymph node (95.8% vs 20%, P = 0.001) and metastasis to the peritoneum except for the diaphragm (97.6% vs 60.0%, P = 0.028) were significantly increased in group A compared with group B. However, no significant differences between the 2 groups were found for rates of histological subtypes (high-grade serous or non-high-grade serous), the presence of ascites, the presence of malignant ascites, exposure of cancer cells on the ovarian surface, blood vascular invasion in the primary lesion, and lymphovascular invasion in the primary lesion.Our study demonstrated that metastasis to the lymph node and nondiaphragmatic metastasis to the peritoneum are significantly associated with metastasis to the diaphragmatic peritoneum, indicating that these factors may be pathological predictors of diaphragmatic metastasis in patients with ovarian cancer. However, as the data available are not sufficient to demonstrate the predictive power of these factors, a further comprehensive, large-scale study should be performed.

Circulating tumor cells as trigger to hematogenous spreads and potential biomarkers to predict the prognosis in ovarian cancer.

Despite several improvements in the surgical field and in the systemic treatment, ovarian cancer (OC) is still characterized by high recurrence rates and consequently poor survival. In OC, there is still a great lack of knowledge with regard to cancer behavior and mechanisms of recurrence, progression, and drug resistance. The OC metastatization process mostly occurs via intracoelomatic spread. Recent evidences show that tumor cells generate a favorable microenvironment consisting in T regulatory cells, T infiltrating lymphocytes, and cytokines which are able to establish an "immuno-tolerance mileau" in which a tumor cell can become a resistant clone. When the disease responds to treatment, immunoediting processes and cancer progression have been stopped. A similar inhibition of the immunosuppressive microenvironment has been observed after optimal cytoreductive surgery as well. In this scenario, the early identification of circulating tumor cells could represent a precocious signal of loss of the immune balance that precedes cancer immunoediting and relapse. Supporting this hypothesis, circulating tumor cells have been demonstrated to be a prognostic factor in several solid tumors such as colorectal, pancreatic, gastric, breast, and genitourinary cancer. In OC, the role of circulating tumor cells is still to be defined. However, as opposed to healthy women, circulating tumor cells have been demonstrated in peripheral blood of OC patients, opening a new research field in OC diagnosis, treatment monitoring, and follow-up.